Process for the production of fluorinated organic compounds and fluorinating agents

ABSTRACT

A process for the production of a fluorinated organic compound, characterized by fluorinating an organic compound having a hydrogen atoms using IF 5 ; and a novel fluorination process for fluorinating an organic compound having a hydrogen atoms by using a fluorinating agent containing IF 5  and at least one member selected from the group consisting of acids, bases, salts and additives.

This is a Divisional Application of U.S. patent application Ser. No.10/296,942, filed on Dec. 10, 2002, now U.S. Pat. No. 6,784,327, whichis a 371 of PCT/JP01/05017, filed on Jun. 13, 2001, which is herebyincorporated by reference.

TECHNICAL FIELD

The present invention relates to a process for fluorinating an organiccompound having a hydrogen atom or hydrogen atoms using IF₅.

BACKGROUND ART

The following are known as fluorinating agents for fluorinating organiccompounds: HF, KF, IF, IF₅, tetrabutylammonium fluoride,tris(dimethylamino)sulfur(trimethylsilyl)difluoride (TASF), SF₄,diethylaminosulfurtrifluoride (DAST), fluorine gas, XeF₂, CF₃OF,CH₃COOF, ClO₃F, N-fluoropyridinium triflate,1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate),1-hydroxy-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate), N-fluorobenzenesulfonimide, etc. (Sheppard, W.A.; Sharts, C. M. Organic Fluorine Chemistry, 1969, W. A. Benjamin:Chambers, R. D.; Fluorine in Organic Chemistry, 1973,Wiley-Interscience: Hudlicky, M. Chemistry of Organic FluorineCompounds, 1976, Ellis Horwood: Hudlicky; M. and Pavlath, A. E.,Chemistry of Organic Fluorine Compounds II, 1995, ACS Monograph 187: N.Ishikawa and Y. Kobayashi, Fluorinated compounds-Chemistry and theirapplication, 1979, Kodansha Ltd.: Outline of chemistry/New fluorinechemistry, 1980, Japan Scientific Societys Press: N. Ishikawa, T.Kitazume, and A. Takaoka, Journal of the Society of Synthetic OrganicChemistry, 1979, 37, 606: T. Umemoto, Journal of the Society ofSynthetic Organic Chemistry, 1992, 50, 338: S. D. Taylor, C. C. Kotoris,and G. Hum; Tetrahedron, 1999, 55, 12431: Japanese Unexamined PatentPublication No. 1997-227531, etc.)

Among those fluorinating agents, HF, KF, IF, tetrabutylammoniumfluoride, and sulfoniumsilicate (TASF) have low reactivity, andtherefore have limited uses. SF₄ is a toxic gas having a boiling pointat −40.4° C., which is difficult to handle. Fluorine gas is so activethat it is difficult to control its reaction. Furthermore, it isreported that CF₃OF, CH₃COOF, and ClO₃F are explosive gases and shouldbe handled with caution. Diethylaminosulfurtrifluoride (DAST), XeF₂,N-fluoropyridinium triflate,1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate),1-hydroxy-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate), N-fluorobenzenesulfonimide, etc., are easy tohandle and enable selective fluorination; however, they are expensivereagents and this causes a problem in using them for industrialpurposes.

IF₅ is an industrially usable fluorinating agent that is a nonexplosiveand easy-to-handle liquid having a boiling point at 100.5° C. and amelting point at 9.4° C. Fluorination using IF₅ is employed only in aprocess of adding IF to perfluoroolefin and substituting iodine of theperfluoroiodoolefin with fluorine (M. Sakai, Organic Fluorine ChemistryI, 1970, pp 348-351, GIHODO SHUPPAN Co., Ltd.: A. A. Banks, H. J.Haszeldine, and V. Kerrigan, J. Chem. Soc., 1948, 2188: R. D. Chambers,W. K. R. Musgrave, and J. Savory, J. Chem. Soc., 1961, 3779). However,since it is difficult to control its high oxidizing property, using IF₅for fluorinating organic compounds that have hydroxyl groups, carbonylgroups, etc., was hitherto not known.

DISCLOSURE OF THE INVENTION

The inventors of the present invention conducted extensive research onthe above problems. Consequently, they found that various kinds oforganic compounds having hydrogen atoms could be fluorinated by usingIF₅.

Specifically, the present invention relates to the following Items 1 to12.

Item 1. A method for producing a fluorinated organic compound byfluorinating an organic compound having hydrogen atoms in the presenceof IF₅.

Item 2. The method for producing a fluorinated organic compoundaccording to Item 1, wherein the organic compound having hydrogen atomsis fluorinated in the presence of IF₅ and HF.

Item 3. The production method according to Item 1, wherein the organiccompound having hydrogen atoms is reacted in the presence of IF₅, HF,and an organic base and/or a room temperature molten salt.

Item 4. The production method according to Item 1, wherein the organiccompound having hydrogen atoms is reacted in the presence of IF₅ and aroom temperature molten salt.

Item 5. The production method according to Item 1, wherein thefluorination reaction does not comprise substitution of bromine oriodine with fluorine, nor an addition reaction of iodine fluoride (IF)to a double bond or triple bond.

Item 6. The production method according to Item 5, wherein thefluorination reaction is conducted in the presence of IF₅ and at leastone member selected from the group consisting of acids, salts, andadditives.

Item 7. The production method according to Item 5, wherein thefluorination reaction is conducted in the presence of IF₅ and at leastone member selected from the group consisting of bases, salts, andadditives.

Item 8. A fluorinating agent for use in fluorinating an organic compoundhaving hydrogen atoms, which comprises IF₅, HF, and an organic baseand/or a room temperature molten salt.

Item 9. A fluorinating agent for use in fluorinating an organic compoundhaving hydrogen atoms, which comprises IF₅ and a room temperature moltensalt.

Item 10. A fluorinating agent for use in fluorinating an organiccompound having hydrogen atoms, which comprises IF₅ and at least onemember selected from the group consisting of acids, salts, andadditives.

Item 11. A fluorinating agent for use in fluorinating an organiccompound having hydrogen atoms, which comprises IF₅ and at least onemember selected from the group consisting of bases, salts, andadditives.

Item 12. A fluorinating agent for use in fluorinating an organiccompound having hydrogen atoms, which comprises IF₅, HF, andtriethylamine.

In the present invention, examples of a organic compound having hydrogenatoms include; compounds having an OH group; ketones (includingdiketone, β-ketocarboxylic acid, β-ketoester); aldehydes; Schiff base,hydrazone and like imines; esters; sulfides; olefins or epoxy; aromaticcompounds (phenylhydrazine derivatives, phenol derivatives, 2-naphtholderivatives, aniline derivatives); and thiocarbonyl compounds, etc.

In fluorine substitution in a organic compound having hydrogen atoms,the following atom and groups are substituted with fluorine: hydrogenatom (CH→CF), carbonyl group (CO→CF₂), hydrazino group (Ph—NHNH₂→Ph—F;C═N—NH₂→CF₂), hydroxyl group (C—OH→C—F), epoxy group (C—O—→C—F), etc.

(1) Compounds Having an OH Group

The following reactions are exemplified:

[in the above formulas, R¹ represents an alkyl group that may have asubstituent, an aralkyl group that may contain a substituent, an alkenylgroup that may contain a substituent, an acyl group that may contain asubstituent, a cycloalkyl group that may contain a substituent, aheterocycloalkyl group that may contain a substituent, or a mono-, di-or tri-saccharide that may contain a protecting group. R^(1a) representsan alkyl group that may contain a substituent, an aryl group that maycontain a substituent, an aralkyl group that may contain a substituent,an alkenyl group that may contain a substituent, an acyl group that maycontain a substituent, a cycloalkyl group that may contain asubstituent, a heterocycloalkyl group that may contain a substituent, ora mono-, di- or tri-saccharide that may contain a protecting group.]

In the present specification, “may contain a substituent” includes bothcases where a substituent is contained and not contained. For example,an alkyl group that may contain a substituent includes alkyl groups andalkyl groups having a substituent.

Specific examples of compounds having an OH group include apliphaticalcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol,isobutanol, tert-butanol, pentanol, hexanol, octanol, decanol, palmitylalcohol, stearyl alcohol, oleyl alcohol, etc., alicyclic alcohols, suchas benzyl alcohol, a mono-, di- or tri-saccharide having at least onenon-protected hydroxyl group, cyclohexyl alcohol, ascorbic acid, etc.,steroid alcohols, such as cholesterol, cholic acid, cortisone, etc.; and

carboxylic acids, such as acetic acid, trifluoroacetic acid, propionicacid, acrylic acid, methacrylic acid, crotonic acid, butyric acid,valeric acid, isovaleric acid, pivalic acid, lauric acid, myristic acid,palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid,cinnamic acid and like aliphatic mono-carboxylic acids, oxalic acid,succinic acid, malonic acid, glutaric acid, adipic acid, maleic acid,fumaric acid, citric acid and like polycarboxylic acids, benzoic acid,salicylic acid, (o-,m-,p-)phthalic acid, nalidixic acid, nicotinic acidand like aromatic carboxylic acids, pantothenic acid, biotin and likevitamins having carboxylic acid groups, glycine, alanine, phenylalanine,cysteine, aspartic acid, glutamic acid, threonine, histidine, lysine,methionine, proline and like 20 kinds of natural amino acids, lacticacid, citric acid, malic acid, tartaric acid and like hydroxycarboxylicacids.

(2) Ketones (Including Diketone, β-Ketocarboxylic Acid, β-Ketoester),Aldehydes, Imines, Such as Schiff Base, Hydrazone, Etc., and Esters

The following reactions are exemplified:

[in the above formulas, X represents O or NR′ (R′ represents a hydrogenatom, an alkyl group that may contain a substituent, an aralkyl groupthat may contain a substituent, an aryl group that may contain asubstituent, an alkenyl group that may contain a substituent, acycloalkyl group that may contain a substituent, a heterocycloalkylgroup that may contain a substituent, a heterocyclic group that maycontain a substituent, an alkoxy group that may contain a substituent,an aryloxy group that may contain a substituent, an amino group, amonoalkylamino group that may contain a substituent, a dialkylaminogroup that may contain a substituent, an acyl group that may contain asubstituent, or an acylamino group that may contain a substituent). R²,R^(2a), and R^(2c) may be the same or different and each represents ahydrogen atom, an alkyl group that may contain a substituent, an aralkylgroup that may contain a substituent, an aryl group that may contain asubstituent, an alkenyl group that may contain a substituent, acycloalkyl group that may contain a substituent, a heterocycloalkylgroup that may contain a substituent, a heterocyclic group that maycontain a substituent, an alkoxy group that may contain a substituent,an aryloxy group that may contain a substituent, a monoalkylamino groupthat may contain a substituent, a dialkylamino group that may contain asubstituent, an acyl group that may contain a substituent, or anacylamino group that may contain a substituent. R² and R^(2a) may bondto each other and form a ring structure. R^(2b) represents an alkylgroup that may contain a substituent, an aralkyl group that may containa substituent, or an aryl group that may contain a substituent.]

Examples of substances having a ring structure include 4-membered rings,5-membered rings, 6-membered rings, and 7-membered rings of aliphaticcompounds that may contain a substitute, etc.

Examples of ketones include acetone, methyl ethyl ketone, acetylacetone,acetoacetic acid, acetoacetate, cyclohexanone, acetophenone,benzophenone, propiophenone, 4-piperidone, 1-oxo-1,2-dihydronaphthalene,benzylideneacetophenone (chalcone), deoxybenzoin, and ketals thereof,etc.

Examples of aldehydes include acetoaldehyde, propionaldehyde,buthylaldehyde, isobutylaldehyde, valeraldehyde, isovaleraldehyde,acrylaldehyde, benzaldehyde, cinnamaldehyde, anisaldehyde,nicotinealdehyde, or acetals thereof, etc.

Examples of imines of Schiff base, hydrazone and the like includecondensates of ketone or aldehyde with an appropriate primary amine.

(3) Sulfides (Including Dithioacetal and Dithioketal)

One or two hydrogen atoms of methylene that is located adjacent to asulfur atom are substituted with fluorine atoms, or a sulfur atom issubstituted with fluorine:

[in the above formulas, R^(3a), R^(3a′), and R^(3a″) may be the same ordifferent and each represents an alkyl group that may contain asubstituent, an aralkyl group that may contain a substituent, an arylgroup that may contain a substituent, an alkenyl group that may containa substituent, a cycloalkyl group that may contain a substituent, aheterocycloalkyl group that may contain a substituent, a heterocyclicgroup that may contain a substituent, or R^(3a) and R^(3a′) bond to eachother and represent a 4-membered ring, 5-membered ring, 6-membered ring,or 7-membered ring of an aliphatic that may contain a substituent. R³and R^(3b) represent an alkyl group that may contain a substituent, anaralkyl group that may contain a substituent, an aryl group that maycontain a substituent, an alkenyl group that may contain a substituent,a cycloalkyl group that may contain a substituent, a heterocycloalkylgroup that may contain a substituent, a heterocyclic group that maycontain a substituent, an alkoxy group that may contain a substituent,an aryloxy group that may contain a substituent, an amino group, amonoalkylamino group that may contain a substituent, a dialkylaminogroup that may contain a substituent, an acyl group that may contain asubstituent, an acylamino group that may contain a substituent, a cyanogroup, an alkylsulfinyl group that may contain a substituent, anaralkylsulfinyl group that may contain a substituent, an arylsulfinylgroup that may contain a substituent, a cycloalkylsulfinyl group thatmay contain a substituent, a heterocycloalkylsulfinyl group that maycontain a substituent, a sulfinyl group bonded by a heterocyclic groupthat may contain a substituent, an alkylsulfonyl group that may containa substituent, an aralkylsulfonyl group that may contain a substituent,an arylsulfonyl group that may contain a substituent, acycloalkylsulfonyl group that may contain a substituent, aheterocycloalkylsulfonyl group that may contain a substituent, or asulfonyl group bonded by a heterocyclic group that may contain asubstituent. Alternately, R³ and R^(3b) may form 4 to 8-membered ringswith carbon atoms with or without having a heteroatom in the ring. Inthe rings, they may be substituted with a halogen atom, an oxo group, analkyl group that may contain a substituent, an aralkyl group that maycontain a substituent, an aryl group that may contain a substituent, analkenyl group that may contain a substituent, a cyano group, or an aminogroup. R^(3c) and R^(3d) represent a hydrogen atom, an alkyl group thatmay contain a substituent, an aralkyl group that may contain asubstituent, an aryl group that may contain a substituent, an alkenylgroup that may contain a substituent, a cycloalkyl group that maycontain a substituent, a heterocycloalkyl group that may contain asubstituent, a heterocyclic group that may contain a substituent, analkoxy group that may contain a substituent, an aryloxy group that maycontain a substituent, a monoalkylamino group that may contain asubstituent, a dialkylamino group that may contain a substituent, anacyl group that may contain a substituent, or an acylamino group thatmay contain a substituent. Alternately, R^(3c) and R^(3d) may form a4-membered ring, 5-membered ring, 6-membered ring or 7-membered ring ofan aliphatic that may contain a substituent, or R^(3c), R^(3d), and Cmay form

R^(3e) represents an alkylene group or an arylene group.]

Examples of sulfides include methyl ethyl sulfide, methyl benzylsulfide, 2-phenylthioacetate, 2-phenylthioacetophenone, C₆H₅—CO—CH₂SCH₃,bis(methylthio)methylbenzene, 2-octyl-1,3-dithiane,2-phenyl-2-trifluoromethyl-1,3-dithiolane, tris(ethylthio)hexane,4-tris(methylthio)toluene, etc.

(4) Olefins or Epoxies

The following fluorine addition reactions are exemplified:

[in the above formula, R⁴, R^(4a), R^(4b), and R^(4c) each represent ahydrogen atom, an alkyl group that may contain a substituent, an aralkylgroup that may contain a substituent, an aryl group that may contain asubstituent, an alkenyl group that may contain a substituent, acycloalkyl group that may contain a substituent, a heterocycloalkylgroup that may contain a substituent, or a heterocyclic group that maycontain a substituent.]

Examples of epoxies include oxirane, 1,2-epoxyethylbenzene,1-chloro-2,3-epoxypropane, α,α′-epoxybibenzyl, etc.

(5) Aromatic Compounds

A fluorine substituent is introduced in an aromatic ring by thefollowing reaction. Fluorination of an aromatic ring in a phenolderivative or aniline derivative can be carried out by fluorinating itusing IF₅ or the like, then reducing it by zinc powder or like reducingagents, to obtain the targeted fluorine compound.

(5-1) Phenylhydrazine Derivatives

A phenylhydrazine residue that may contain a substituent can besubstituted with a fluorine atom.

[in the above formula, R^(5a), R^(5b), R^(5c), R^(5d), and R^(5e) eachrepresents a hydrogen atom, an alkyl group, an aralkyl group, an arylgroup, an alkoxy group, a nitro group, a cyano group, a halogen atom, anacyl group, an amino group, a monoalkylamino group, a dialkylaminogroup, an acylamino group, or an alkylthio group.](5-2) Phenol Derivatives

A phenol derivative forms the difluorinated quinonoid structure as shownbelow by reacting with IF₅. Thereafter, by reducing the resultantcompound, a phenol derivative having fluorine introduced in the ortho-or para-position is produced.

[in the above formulas, R^(5a), R^(5b)R^(5c) and R^(5d) each representsa hydrogen atom, an alkyl group, an aralkyl group, an aryl group, analkoxy group, a nitro group, a cyano group, a halogen atom, an acylgroup, an amino group, a monoalkylamino group, a dialkylamino group, anacylamino group, or an alkylthio group.]

In a starting material in which all atoms or groups in the ortho- andpara-positions are substituted, fluorine atoms are introduced into theortho- or para-position, forming compounds having a fluorine quinonoidstructure (e.g., Example 47).

In the above example, phenol that may contain a substituent is used as aphenol derivative; however, it is also possible to introduce fluorineatoms into benzene-based aromatic compounds or condensed polycyclichydrocarbons that may be substituted and have electron-releasing groupssuch as a hydroxyl group, an alkoxy group, etc.

(5-3) 2-naphthol Derivatives

A carbon atom in the 1-position of naphthol can be subjected to mono- ordi-fluorination.

[in the above formulas, R^(5a), R^(5b), R^(5c), R^(5d), R^(5e), R^(5f),and R^(g) may be the same or different and each represents a hydrogenatom, an alkyl group, an aralkyl group, an aryl group, an alkoxy group,a nitro group, a cyano group, a halogen atom, an acyl group, an aminogroup, a monoalkylamino group, a dialkylamino group, an acylamino group,or an alkylthio group.](5-4) Aniline Derivatives

Similar to a phenol derivative, an aniline derivative forms thedifluorinated quinonoid structure as shown below by reacting with IF₅.Then, by reducing the resultant compound, an aniline derivative havingfluorine introduced in the ortho- or para-position is produced.

[in the above formulas, R^(5a), R^(5b), R^(5c), and R^(5d) eachrepresents a hydrogen atom, an alkyl group, an aralkyl group, an arylgroup, an alkoxy group, a nitro group, a cyano group, a halogen atom, anacyl group, an amino group, a monoalkylamino group, a dialkylaminogroup, an acylamino group, or an alkylthio group.]

Using aniline that may contain a substituent or naphthylamine that maycontain a substituent as an aniline derivative also allows introducing afluorine atom in an aromatic ring.

(6) Thiocarbonyl Compounds (Including Thioketone, Thioester,Thiocarbonic Ester, Thioamide, Dithiocarboxylate, and Dithiocarbamate)

The following reactions are exemplified:

[in the above formulas, R⁶ and R^(6a) may be the same or different andeach represents a hydrogen atom, an alkyl group that may contain asubstituent, an aralkyl group that may contain a substituent, an arylgroup that may contain a substituent, an alkenyl group that may containa substituent, a cycloalkyl group that may contain a substituent, aheterocycloalkyl group that may contain a substituent, a heterocyclicgroup that may contain a substituent, an alkoxy group that may contain asubstituent, an aryloxy group that may contain a substituent, amonoalkylamino group that may contain a substituent, a dialkylaminogroup that may contain a substituent, an acyl group that may contain asubstituent, or an acylamino group that may contain a substituent. R⁶and R^(6a) may bond to each other and form a ring structure. R^(6b)represents an alkyl group that may contain a substituent, an aralkylgroup that may contain a substituent, an aryl group that may contain asubstituent, an alkenyl group that may contain a substituent, acycloalkyl group that may contain a substituent, a heterocycloalkylgroup that may contain a substituent, or a heterocyclic group that maycontain a substituent.]

Examples of thiocarbonyl compounds include O-methylcyclohexanecarbothioate, O-propyl 1-piperidinecarbothioate, methyldithiobenzoate, thiobenzophenone, O-phenyl thiobenzoate,N,N-dimethylphenylthioamide, ethyl 3-quinolinedithiocarboxylate,trifluoromethane carbothioylnaphthalene, N-methyl-N-phenyltrifluoromethanethioamide, N-benzyl-N-phenylheptafluoropropanethioamide,

etc.

Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl,nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl,hexadecyl, heptadecyl, octadecyl and like C₁-C₁₈ alkyl groups havingstraight chains or branched chains, preferably methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl andlike C₁-C₆ alkyl groups having straight chains or branched chains.

Examples of alkoxy groups include methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy,hexyloxy and like C₁-C₆ alkoxy groups having straight chains or branchedchains.

Examples of alkenyl groups include a vinyl group, an allyl group, a3-butenyl group and like C₂-C₆ alkenyl groups, etc.

Examples of halogens include a fluorine atom, a chlorine atom, a bromineatom, an iodine atom, etc.

Examples of aryl groups include a phenyl group, a naphthyl group, etc.

Examples of aryloxy groups include a phenoxy group, a naphthyloxy group,etc.

Examples of aralkyl groups include 2-phenylethyl, benzyl, 1-phenylethy,3-phenylpropyl, 4-phenylbutyl and like C₁-C₁₀ aralkyl groups, etc.

Examples of cycloalkyl groups include cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and like C₃-C₈cycloalkyl groups, etc. Preferable are C₃-C₇ cycloalkyl groups.

Examples of heterocycloalkyl groups include substances in which one ormore carbon atoms forming the above described ring structure ofcycloalkyl groups are substituted with atoms of nitrogen, oxygen,sulfur, etc.

Examples of monoalkylamino groups include amino groups mono-substitutedwith the above-described C₁-C₆ alkyl groups.

Examples of dialkylamino groups include dimethylamino, diethylamino,di-n-propylamino, diisopropylamino, dibutylamino, dipentylamino,dihexylamino and like amino groups di-substituted with theabove-described C₁-C₆ alkyl groups.

Examples of acylamino groups include formylamino, benzoylamino,acetylamino, propionylamino, n-butyrylamino and like C₁-C₈ acylaminogroups.

Examples of alkylthio groups include —S—(C₁-C₆ alkyl groups), etc.(C₁-C₆ alkyl groups are the same as described above.)

Examples of heterocyclic groups include piperidyl, furyl, thienyl,imidazolyl, oxazolyl, thiazolyl, pyrrolyl, pyrrolidinyl, triazolyl,benzothiazolyl, benzoimidazolyl, oxadiazolyl, thiadiazolyl, indolyl,pyrazolyl, pyridazinyl, cinnolinyl, quinolinyl, isoquinolinyl,quinoxalinyl, pyradinyl, pyridyl, benzofuryl, benzothienyl, tetrazolyl,etc.

Examples of acyl groups include formyl, acetyl, propionyl, n-butyryl,isobutyryl, valeryl, isovaleryl, pivaloyl and like C₁₋₆ acyl groupshaving straight chains or branched chains, benzoyl and a substitutedacyl group.

Specific examples of an alkyl group, an aralkyl group, an aryl group, acycloalkyl group, a heterocycloalkyl group, and a heterocyclic group inan alkylsulfinyl group, an aralkylsulfinyl group, an arylsulfinyl group,a cycloalkylsulfinyl group, a heterocycloalkylsulfinyl group, and asulfinyl group having a heterocyclic group bonded thereto are asdescribed above.

Specific examples of an alkyl group, an aralkyl group, an aryl group, acycloalkyl group, a heterocycloalkyl group, and a heterocyclic group inan alkylsulfonyl group, an aralkylsulfonyl group, an arylsulfonyl group,a cycloalkylsulfonyl group, a heterocycloalkylsulfonyl group, and asulfonyl group having a heterocyclic group bonded thereto are asdescribed above.

The number of substituents in an alkyl group having substituents, analkoxy group having substituents, or an alkenyl group havingsubstituents is generally 1 to 5, and preferably 1 to 3. Examples ofsubstituents include halogen, C₁-C₆ alkoxy, C₁-C₆ alkylthio, cyano,nitro, an amino group, a hydroxyl group and the like. Examples of analkyl group having halogens include an alkyl group in which one or morehydrogen atoms are substituted with fluorine.

The number of substituents in an aralkyl group having substituents, anaryl group having substituents, an aryloxy group having substituents, acycloalkyl group having substituents, a heterocycloalkyl group havingsubstituents, a heterocyclic group having substituents, a monoalkylaminogroup having substituents, a dialkylamino group having substituents, anacylamino group having substituents, an alkylsulfinyl group havingsubstituents, an aralkylsulfinyl group having substituents, anarylsulfinyl group having substituents, a cycloalkylsulfinyl grouphaving substituents, a heterocycloalkylsulfinyl group havingsubstituents, a sulfinyl group to which a heterocyclic group havingsubstituents is bonded, an alkylsulfonyl group having substituents, anaralkylsulfonyl group having substituents, an arylsulfonyl group havingsubstituents, a cycloalkylsulfonyl group having substituents, aheterocycloalkylsulfonyl group having substituents, or a sulfonyl groupto which a heterocyclic group having substituents is bonded is generally1 to 5, preferably 1 to 3. Examples of substituents include C₁-C₆ alkylgroups, a halogen atom, C₁-C₆ alkoxy groups, C₁-C₆ alkylthio groups,cyano, nitro, an amino group, a hydroxyl group and the like.

The number of substituents in a 4- to 7-membered ring of aliphaticshaving substituents is generally 1 to 5, and preferably 1 to 3. Examplesof substituents include C₁-C₆ alkyl groups, a halogen atom, C₁-C₆ alkoxygroups, C₁-C₆ alkylthio groups, cyano, nitro, an amino group, a hydroxylgroup, carboxy ester and the like. In addition,

is also included in 4- to 7-membered ring of aliphatics havingsubstituents.

Examples of acyl groups having substituents include a chloroacetylgroup, a bromoacetyl group, a dichloroacetyl group, a trifluoroacetylgroup and like substituted acetyl groups, a methoxyacetyl group, anethoxyacetyl group and like acetyl groups substituted with alkoxygroups, a methylthioacetyl group and like acetyl groups substituted withalkylthio groups, a phenoxyacetyl group, a phenylthioacetyl group, a2-chlorobenzoyl group, a 3-chlorobenzoyl group, a 4-chlorobenzoyl group,a 4-methylbenzoyl group, a 4-t-butylbenzoyl group, a 4-methoxybenzoylgroup, a 4-cyanobenzoyl group, a 4-nitrobenzoyl group and likesubstituted benzoyl groups, etc.

As for the production method and fluorinating agents of the presentinvention, it is preferable to use, in addition to IF₅, 1 to 4 membersand preferably 1 to 3 members selected from the group consisting ofacids, bases, salts and additives. More preferably, 1 to 3 membersexcept for the combination of an acid, a basic and a salt are used.

Specific examples of acids include sulfuric acid, nitric acid,phosphoric acid, polyphosphoric acid, hydrogen fluoride, fluoric acid,hydrochloric acid, hydrogen bromide, hydrogen iodide, hypochlorous acid,chlorous acid, chloric acid, perchloric acid, perbromic acid, periodicacid and like hydrogen halides, or hydrohalic acid, hypohalous acid,halous acid, halogen acid, and perhalogen acid;

fluorosulfonic acid, chlorosulfonic acid, methanesulfonic acid,ethanesulfonic acid, trifluoromethanesulfonic acid,difluoromethanesulfonic acid, trichloromethanesulfonic acid,perfluorobutanesulfonic acid, perfluorooctanesulfonic acid,benzenesulfonic acid, toluenesulfonic acid, nitrobenzenesulfonic acidand like sulfonic acids, or polystyrenesulfonic acid, fluorinatedsulfonic acid resin (Nafion-H) and like polymer carrying sulfonic acids;

formic acid, acetic acid, propionic acid, chloroacetic acid, bromoaceticacid, dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid,glycolic acid, lactic acid, benzoic acid, oxalic acid, succinic acid andlike mono- or poly-carboxylic acids;

SO₃, BF₃, BCl₃, B(OCH₃)₃, AlCl₃, AlBr₃, SbF₃, SbCl₃, SbF₅, PF₃, PF₅,AsF₃, AsCl₃, AsF₅, TiCl₄, NbF₅, TaF₅ and like Lewis acids or their ethercomplexes;

HBF₄, HPF₆, HAsF₆, HSbF₆, HSbCl₆ and like acids formed between Lewisacids and hydrogen halides, or their ether complexes;

or mixtures of two or more members described above. The acids used heremay be supported by several kinds of carriers. Examples of carriersinclude SiO₂, methylated SiO₂, Al₂O₃, Al₂O₃—WB, MoO₃, ThO₂, ZrO₂, TiO₂,Cr₂O₃, SiO₂—Al₂O₃, SiO₂—TiO₂, SiO₂—ZrO₂, TiO₂—ZrO₂, Al₂O₃—B₂O₃,SiO₂—WO₃, SiO₂—NH₄F, HSO₃Cl—Al₂O₃, HF—NH₄—Y, HF—Al₂O₃, NH₄F—SiO₂—Al₂O₃,AlF₃—Al₂O₃, Ru—F—Al₂O₃, F—Al₂O₃, KF—Al₂O₃, AlPO₄, AlF₃, bauxite, kaolin,activated carbon, graphite, Pt-graphite, ion-exchange resin, metalsulfate, chloride, Al and like metals, Al—Mg, Ni—Mo and like alloys,polystyrene and like polymers, etc.

The amount of the above-described acids used in the present inventioncan be selected from a catalytic amount to an excessive amount. Thepreferable amount is 0.01 to 100 moles, and more preferably 0.1 to 20moles per mole of the organic compound containing a hydrogen atom to befluorinated. It is also possible to use the above-described acids as areaction solvent. In this case, the amount of solvent used can beselected from little to excessive.

The bases or organic bases used in the present invention include theones generally used, such as sodium hydroxide, potassium hydroxide,lithium hydroxide, rubidium hydroxide, cesium hydroxide, magnesiumhydroxide, calcium hydroxide, barium hydroxide and like hydroxides ofalkali metals or alkaline earth metals;

sodium methoxide, sodium ethoxide, sodium butoxide, potassium methoxide,potassium ethoxide, potassium butoxide, lithium methoxide, lithiumethoxide and like alkali metal alkoxides;

sodium hydride, potassium hydride, lithium hydride, calcium hydride andlike hydrides of alkali metals or alkaline earth metals;

sodium, potassium, lithium and like alkali metals;

magnesium oxide, calcium oxide and like alkaline earth metal oxides;

ammonia, ammonium hydroxide, tetramethylammonium hydroxide,tetraethylammonium hydroxide, tetrabuthylammonium hydroxide,octyltriethylammonium hydroxide, benzyltrimethylammonium hydroxide andlike ammonium hydroxide salts, or AMBERLITE® resin and like polymercarrying ammonium hydroxide salts, etc.;

aliphatic amine (primary amine, secondary amine, tertiary amine),alicyclic amine (secondary amine, tertiary amine), aromatic amine(primary amine, secondary amine, tertiary amine), heterocyclic amine andlike organic bases; and mixtures thereof.

Specific examples of aliphatic primary amines include methylamine,ethylamine, propylamine, butylamine, pentylamine, hexylamine,cyclohexylamine, ethylenediamine, etc. Specific examples of aliphaticsecondary amines include dimethylamine, diethylamine, dipropylamine,dibutylamine, dipentylamine, dihexylamine, dicyclohexylamine, etc.Specific examples of aliphatic tertiary amines include trimethylamine,triethylamine, diisopropylethylamine,N,N,N′,N′-tetramethylethylenediamine, etc.

Specific examples of alicyclic secondary amines include piperidine,piperazine, pyrrolidine, morpholine, etc. Specific examples of alicyclictertiary amines include N-methylpiperazine, N-methylpyrrolidine,5-diazabicyclo[4.3.0]nonane-5-ene, 1,4-diazabicyclo[2.2.2]octane, etc.

Specific examples of aromatic amines include aniline, methylaniline,dimethylaniline, N,N-dimethylaniline, haloaniline, nitroaniline, etc.

Specific examples of heterocyclic amines include pyridine, pyrimidine,piperazine, quinoline, imidazole, etc., and further include polyarylamine, polyvinylpyridine and like polymer carrying amine compounds,etc., and mixtures thereof.

The amount of the above-described bases used in the present inventioncan be selected from a catalytic amount to an excessive amount. Thepreferable amount of the bases used is 0.01 to 20 moles, and morepreferably 0.1 to 10 moles per mole of the organic compound containing ahydrogen atom to be fluorinated.

In the present invention, when an acid as a reaction solvent, and ametal, metal hydroxide, metal hydride, metal alkoxide, metal oxide, ororganic base as a base are used, a metal salt of an acid or a salt of anorganic base is naturally produced from a reaction between the acid andbase.

The salts used in the present invention are compounds generated by areaction between an acid and a base, and mainly include the compoundsobtained by the reaction between the above-mentioned acids and bases.

For example, metal salts or ammonium salts of sulfuric acids or sulfonicacids, such as sodium sulfate, sodium hydrogensulfate, potassiumsulfate, potassium hydrogensulfate, lithium sulfate, cesium sulfate,calcium sulfate, magnesium sulfate, ammonium sulfate, triethylammoniumsulfate, pyridinium sulfate, trimethylpyridinium sulfate,polyarylammonium sulfate, polyvinylpyridinium sulfate, sodiummethanesulfonate, ammonium methanesulfonate, tetramethylammoniummethanesulfonate, potassium ethanesulfonate, lithium butanesulfonate,sodium benzenesulfonate, sodium toluenesulfonate, sodiumtrifluoromethanesulfonate, sodium polystyrenesulfonate, etc.;

sodium formate, ammonium formate, sodium acetate, potassium acetate,lithium acetate, magnesium acetate, calcium acetate, ammonium acetate,methylammonium acetate, diethylammonium acetate, triethylammoniumacetate, tetraethylammonium acetate, pyridinium acetate, sodiumpropionate, potassium propionate, sodium butyrate, polyarylammoniumbutyrate, polyvinylpyridinium acetate, sodium isobutyrate, sodiumvalerianate, sodium nonanoate, sodium chloroacetate, sodiumbromoacetate, sodium trichloroacetate, sodium trifluoroacetate, sodiumglycolate, sodium lactate, sodium benzoate, sodium oxalate, sodiumsuccinate, sodium polyacrylate and like metal salts or ammonium salts ofcarboxylic acids;

LiBr, LiI, NaBr, NaI, KBr, KI, RbBr, RbI, CsBr, CsI, BeBr₂, BeI₂, MgBr₂,MgI₂, CaBr₂, CaI₂, SrBr₂, SrI₂, BaBr₂, BaI₂, ZnBr₂, ZnI₂, CuBr₂, CuI₂,CuBr, CuI, AgBr, AgI, AuBr, AuI, NiBr₂, NiI₂, PdBr₂, PdI₂, PtBr₂, PtI₂,CoBr₂, CoI₂, FeBr₂, FeBr₃, FeI₂, FeI₃, MnBr₂, MnI₂, CrBr₂, CrI₂, PbBr₂,PbI₂, SnBr₂, SnI₂, SnBr₄, SnI₄ and like metal salts;

NH₄Br, NH₄I, MeNH₃Br, MeNH₃I, Me₄NBr, Me₄NI, Et₄NBr, Et₄NI, Bu₄NBr,Bu₄NI, PhMe₃NBr, PhMe₃NI, PhCH₂NMe₃I, pyridinium bromide, pyridiniumiodide, chloropyridinium iodide, methylpyridinium iodide,cyanopyridinium iodide, bipyridinium iodide, quinolium iodide,isoquinolium iodide, N-methylpyridinium bromide, N-methylpyridiniumiodide, N-methylquinolium iodide and like pyridinium salts or ammoniumsalts;

Me₄PBr, Me₄PI, Et₄PI, Pr₄PI, Bu₄PBr, Bu₄PI, Ph₄PBr, Ph₄PI and likephosphonium salts;

sodium fluoride, potassium fluoride, cesium fluoride, ammonium fluoride,tetraethylammonium fluoride, tetrabutylammonium fluoride,polyarylammonium fluoride, sodium chloride, ammonium chloride, sodiumhypochlorous acid, sodium chlorite, sodium chlorate, sodium perchlorate,sodium perbromate, sodium periodate and like metal salts or amine saltsof hydrogen halides, hypohalous acids, halous acids, halogen acids, orperhalogen acids;

sodium carbonate, potassium carbonate, lithium carbonate, sodiumhydrogencarbonate, potassium hydrogencarbonate, lithiumhydrogencarbonate, calcium carbonate, magnesium carbonate and likecarbonates;

sodium phosphate, potassium phosphate, sodium hydrogenphosphate, sodiumdihydrogenphosphate, ammonium phosphate, pyridinium phosphate and likemetal salts or amine salts of phosphoric acid;

sodium nitrate, potassium nitrate, ammonium nitrate, pyridinium nitrateand like metal salts or amine salts of nitric acid;

NaBF₄, KBF₄, LiBF₄, NaSbF₆, NaAsF₆, NaPF₆, NH₄BF₄, NH₄SbF₆, NH₄PF₆ andlike metal salts or amine salts formed between Lewis acids and hydrogenhalide;

tetramethylphosphonium fluoride, tetramethylphosphonium acetate,tetraphenylphosphonium fluoride and like phosphonium salts;

(C₂H₅)₄NF, 1-ethyl-3-methylimidazolium fluoride, (C₂H₅)₃N—(HF)_(n),(C₂H₅)₄NF—(HF)_(n), (n-C₄H₉)₃N—(HF)_(n), (n-C₄H₉)₄NF—(HF)_(n),BF₃.Et₂O—(HF)_(n), when (n=1 to 20), and like room temperature moltensalts having fluoride anions or HF;

and mixtures thereof.

Examples of the additives used in the present invention include halogen,interhalogen compounds, polyhalides and the like. Specific examples ofhalogens include iodine, bromine, chlorine, etc. Among those, iodine andbromine are preferable, and iodine is more preferable. Specific examplesof the interhalogen compounds include one, two or more members of ClF,BrF, ICl, IBr, I₂Cl₆, ICl₃, but are not limited to them. Specificexamples of the polyhalides include one, two or more members of LiCl₄I,NaCl₄I, KCl₄I, CsCl₄I, RbCl₄I, Me₄NCl₄I, Et₄NCl₄I, Pr₄NCl₄I, Bu₄NCl₄I,PhNMe₃Cl₄I, PhCH₂NMe₃Cl₄I, Me₃SCl₄I, Cl₈IP, KCl₃I₂, Me₄NCl₃I₂,2,2′-bipyridinium μ-chlorodichlorodiiodate, 2,2′-biquinoliniumμ-chlorodichlorodiiodate, KCl₂I, Me₄NCl₂I, Me₄NClI₂, Et₄NCl₃, Ph₄AsCl₃,KClF₂, Me₄NClF₄, CsClF₄, CsCl₃FI, KBrClI, NH₄BrClI, Me₄NBrClI,Me₄NBrCl₂, Bu₄NBrCl₂, Me₄NBrCl₂I₂, CsBrFI, NaBrF₂, KBrF₂, CsBrF₄,Me₄NBrF₄, CsBrF₆, Me₄NBrF₆, Et₄NBr₆Cl, CsBr₃, Me₄NBr₃, Et₄Br₃, Bu₄NBr₃,PhCH₂NMe₃Br₃, pyridinium tribromide, Br₇P, CsBrI₂, Me₄NBrI₂, Me₄NBrI₄,Me₄NBrI₆, KBr₂Cl, Me₄NBr₂Cl, Bu₄NBr₂Cl, KBr₂I, Me₄NBr₂I, Bu₄NBr₂I,2,2′-bipyridinium μ-bromodibromodiiodate, NaF₂I, KF₂I, CsF₄I, CsF₆I,CsF₈I, KI₃, CsI₃, Me₄NI₃, Et₄NI₃, Pr₄NI₃, Bu₄NI₃, pyridinium triiodide,Me₄NI₅, Et₄NI₇, Me₄NI₉, Me₄PBr₃, Me₄PI₃, Me₄PIBr₂, Me₄PICl₂, Et₄PI₃,Bu₄PI₃, Ph₄PI₃, Ph₄PBr₃, Ph₄PIBr₂, but are not limited to them.

In the production method of the present invention, IF₅ can be used inthe amount of 0.2 to 20 moles, preferably 0.3 to 5 moles, and morepreferably 0.4 to 2 moles per mole of organic compound having a hydrogenatom and additives can be used in an amount from 0.1 to 10 times (molarratio) based on the organic compound to react at −70° C. to 200° C., andpreferably −20° C. to 100° C.

Use of a reaction solvent is not necessary, but preferably it is used.Specific examples of the reaction solvents include pentane, hexane,heptane, cyclohexane, petroleum ether and like aliphatic solvents,dichloromethane, dichloroethane, chloroform, fluorotrichloromethane,1,1,2-trichlorotrifluoroethane,2-chloro-1,2-dibromo-1,1,2-trifluoroethane,1,2-dibromohexafluoropropane, 1,2-dibromotetrafluoroethane,1,1-difluorotetrachloroethane, 1,2-difluorotetrachloroethane,heptafluoro-2,3,3-trichlorobutane,1,1,1,3-tetrachlorotetrafluoropropane,1,1,1-trichloropentafluoropropane, 1,1,1-trichlorotrifluoroethane,polychlorotrifluoroethylene and like aliphatic halide solvents, methylformate, ethyl formate, methyl acetate, ethyl acetate, propyl acetate,methyl propionate, γ-butyrolactone, propylene carbonate and like estersolvents, acetonitrile, propionitrile and like nitrile solvents,benzene, chlorobenzene, toluene, dichlorobenzene, fluorobenzene,nitrobenzene and like aromatic solvents, diethylether, dipropylether,tetrahydrofuran and like ether solvents, N,N-dimethyl formamide(DMF),dimethylsulfoxide (DMSO), water, nitromethane, N,N-diethylformamide,N,N-dimethylacetamide, 1-methyl-2-pyrrolidone,1,3-dimethyl-2-imidazolidinone (DMI), tetramethylurea,1,3-dimethylpropyleneurea, hexamethylphosphoramide (HMPA), etc. They areused singularly or as a mixture of two or more members.

The order of adding organic compounds and IF₅, acids, bases, salts, oradditives can be arbitrary so far as long time intervals do not existbetween them.

As for postprocessing after the reaction, it is possible to add variouskinds of organic or inorganic reducing agents to reduce the excessivelyoxidized organic compounds, or to reduce IF₅ or the oxidative compoundsderived from IF₅ that remain in an excessive amount.

Specific examples of such reducing agents include zinc powder, tin, tinchloride, iron, aluminium, sodium thiosulphate, butyltinhydride, sodiumborohydride, lithium aluminium hydride, etc.; however, as long as theyare reductive compounds, the reducing agents are not limited to theabove examples.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be explained in more detail referring to theExamples and Comparative Examples given below. However, the scope of thepresent invention is not limited to these examples.

Example

Organic compounds having hydrogen atoms, which serve as startingmaterials, are fluorinated using IF₅ under the conditions listed inTables 1 to 6 shown below. The results are shown in Tables 1 to 6.

The reaction conditions of reaction Methods A, B, C, D, D′, E, F, G, H,I, and J are described below.

Method A

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (1.2 mmol) and a reactionsolvent (4 ml) were held in a PFA vessel (15 ml). While stirring at roomtemperature, a substrate (1.0 mmol) was added hereinto, and allowed toreact at a predetermined temperature for a predetermined period of time.After the completion of the reaction, the reaction mixture solution wasneutralized by a sodium bicarbonate aqueous solution, and reduced by a10% sodium thiosulphate aqueous solution. The resultant product wasextracted by ether, and isolated and purified using columnchromatography. The resultant product was analyzed based on NMR, IR, andMS, and the reaction yield was obtained as the isolation yield of theresultant product against the substrate. In Methods B to E and H to J,postprocessing and analysis after the completion of reaction wereconducted in the same manner as that of Method A.

Method B

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (1.2 mmol) and a reactionsolvent (2 ml) were held in a PFA vessel (15 ml). While stirring at roomtemperature, a substrate (1.0 mmol) dissolved in a reaction solvent (2ml) was added hereinto, and allowed to react at a predeterminedtemperature for a predetermined period of time.

Method C

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (1.2 mmol) and a reactionsolvent (2 ml) were held in a PFA vessel (15 ml). While stirring at −78°C., a substrate (1.0 mmol) dissolved in a reaction solvent (2 ml) wasadded, and then allowed to react at room temperature for a predeterminedperiod of time.

Method D

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (1.2 mmol) and a solvent (20ml) were held in a PFA vessel (100 ml). While stirring at roomtemperature, a substrate (1.0 mmol) dissolved in a reaction solvent (20ml) was added hereinto using a dropping apparatus in one hour andstirred for one hour.

Method D′

After the completion of the reaction of Method D, 3N of HCl aqueoussolution (20 ml) was added to an organic layer washed with water, andstirred using an excessive amount of Zn powder (room temperature, onehour). After filtering solid substances, isolation and purification wasperformed.

In the Method column on Tables 1 to 6, the asterisk (*) indicates that,instead of the IF₅/Et₃N-3HF (1:1 molar ratio) solution, an IF₅ (1.2mmol)/CH₂Cl₂ (0.46 g) solution was used.

In the tables, “*2” indicates that, instead of the IF₅/Et₃N-3HF (1:1molar ratio) solution, an IF₅/Et₄NF (1:1 molar ratio) solution was used,and “*3” indicates that instead of the IF₅/Et₃N-3HF (1:1 molar ratio)solution, an IF₅/Et₃N-5HF (1:1 molar ratio) solution was used.

Method E

IF₅ (1.2 mmol) and a solvent (4 ml) were held in a PFA vessel (20 ml).While stirring at room temperature, Et₃N (1.2 mmol) was added droppwise.Five minutes later, a substrate (1.0 mmol) was added and stirred at roomtemperature for three hours. After adding 2-fluoronitrobenzene (1.0mmol) to the reaction solution as an internal standard, a portion of thereaction solution was taken out and diluted by acetonitrile-d3, and theyield of the fluorinated substance was obtained by ¹⁹F-NMR.

Method F

IF₅/Et₃N-3HF (1.2 mmol) and a solvent (10 ml) were held in a PFA vessel(100 ml) and heated to 40° C. Then, 10 ml of a solvent solution of asubstrate (1.0 mmol) was added thereinto and stirred at 40° C. for 30minutes. After cooling, fluorobenzene (1.0 mmol) was added to thereaction solution as an internal standard, a portion of the reactionsolution was taken out and diluted by acetonitrile-d3, and the yield ofthe fluorinated substance was obtained by ¹⁹F-NMR.

Method G

IF₅/Et₃N-3HF (1.5 mmol), iodine (3.0 mmol), and a solvent (30 ml) wereheld in a PFA vessel (100 ml). Under an ice-cold atmosphere, a substrate(1.0 mmol) dissolved in 10 ml of solvent was added thereinto and stirredunder the ice-cold atmosphere for 30 minutes and at room temperature for30 minutes. After cooling, fluorobenzene (1.0 mmol) was added to thereaction solution as an internal standard, and then a portion of thereaction solution was taken out and diluted by acetonitrile-d3, and theyield of the fluorinated substance was obtained by ¹⁹F-NMR.

Method H

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (1.2 mmol) and reactionsolvent (8 ml) were held in a PFA vessel (15 ml). While stirring at roomtemperature, a substrate (1.0 mmol) was added thereinto and allowed toreact at a predetermined temperature for a predetermined period of time.

Method I

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (1.2 mmol) and a reactionsolvent (4 ml) were held in a PFA vessel (15 ml). While stirring at roomtemperature, a substrate (1.0 mmol) dissolved in a reaction solvent (4ml) was added thereinto and allowed to react at a predeterminedtemperature for a predetermined period of time.

Method J

An IF₅/Et₃N-3HF (1:1 molar ratio) solution (5.0 mmoles) and a reactionsolvent (4 ml) were held in a PFA vessel (15 ml). While stirring at roomtemperature, a substrate (1.0 mmol) was added thereinto and allowed toreact at a predetermined temperature for a predetermined period of time.

The ¹⁹F-NMR signals (F, δ ppm) of IF₅/3HF and IF₅/Et₃N/3HF are shownbelow.IF₅/3HF  (1)IF₅(1F, 55 ppm), (4F, 6.4 ppm), HF(3F, −194 ppm)IF₅/Et₃N/3HF  (2)Measuring temperature: 25° C.

One wide single peak was observed at the δ value of −53 ppm.

Measuring temperature: −40° C.

Two wide single peaks were observed at the δ values of 7.5 ppm and −160ppm. (Integration ratio: approximately 1:1)

Measuring temperature: −60° C.

Three wide single peaks were observed at the δ values of 3 ppm, −154ppm, and −162 ppm. (Integration ratio:approximately 2:1:1)

From comparison of the ¹⁹F-NMR signals of IF₅/3HF and IF₅/Et₃N/3HF, thecompounds generated from IF₅/Et₃N/3HF have complexes formed therein.

Spectrum data of the compounds obtained by the present invention areshown below. Regarding the compounds for which spectrum data is notshown, it was confirmed that the targeted compounds were obtained bycomparing the spectrum data obtained in the Examples of the presentinvention with the known spectrum data.

-   Tetradecanoyl fluoride:

¹H-NMR (CDCl₃) δ 0.88 (3H, t, J=6.7 Hz), 1.25-1.32 (20H, m), 1.64-1.71(2H, m), 2.50 (2H, t, J=7.3 Hz);

¹⁹F-NMR (CDCl₃) δ 44.8 (s);

IR (neat, cm⁻¹) 2925, 2854, 1845, 1467, 1081.

-   4-Fluoro-2,6-dimethyl-phenylamine:

¹H-NMR (CDCl₃) δ 2.16 (6H, s), 3.42 (2H, bs), 6.67 (2H, d, J=9.2 Hz);

¹⁹F-NMR(CDCl₃) δ −128.3 (1F, t, J=9.2).

-   2,6-Di-tert-butyl-4-fluoro-phenol:

¹H-NMR (CDCl₃) δ: 1.42 (18H, s); 4.94(1H, s); 6.87 (2H, d, J=10.2 Hz);

¹⁹F-NMR(CDCl₃) δ: −124.7 (1F, t, J=10.2);

IR (neat, cm⁻¹); 3642; 2961; 1599; 1428; 1236; 1149; 964; 867; 776;

MS m/z: 224 (M⁺); 209 (M⁺-Me); 57;

HRMS Calc. for C₁₄H₂₁OF: m/z 224.1576. Found: m/z 224.1571.

-   2,4,6-Tri-tert-butyl-4-fluoro-cyclohexa-2,5-dienone:

¹H-NMR (CDCl₃) δ 0.99 (9H, s), 1.24 (18H, s), 6.63 (2H, d, J=10.5 Hz);

¹⁹F-NMR(CDCl₃) δ −96.6 (1F, t, J=10.3 Hz);

IR (KBr, cm⁻¹) 2958, 2873, 1734, 1670, 1138, 1650, 1461, 1364, 1272,1123, 1073, 965.

-   (1-Fluoro-1-methyl-pentyl)-phenyl-diazene:

¹H-NMR (CDCl₃) δ 0.90 (3H, t, J=7.1 Hz), 1.30-1.55 (4H, m), 1.57 (3H, d,J=20.0 Hz), 168-1.13 (2H, m), 7.47-7.50 (3H, m), 7.74-7.78 (2H, m);

¹⁹F-NMR(CDCl₃) δ −130.1-129.2 (1F, m);

IR (neat, cm⁻¹) 2957, 1526, 1455, 1141, 765, 689.

-   tert-Butyl-(1-fluoro-1-methyl-pentyl)-diazene:

¹H-NMR (CDCl₃) δ 0.89 (3H, t, J=7.1 Hz), 1.22 (9H, s), 1.23-1.35 (4H,m), 1.39 (3H, d, J=20.0 Hz), 1.68-1.88 (2H, m);

¹⁹F-NMR(CDCl₃) δ −130.9-131.2 (1F, m);

IR (neat, cm⁻¹) 2965, 1457, 1364, 1230, 1149, 905.

-   tert-Butyl-(difluoro-p-tolyl-methyl)-diazene:

¹H-NMR (CDCl₃) δ 1.24 (9H, s), 2.37 (3H, s), 7.22 (2H, d, J=8.1 Hz),7.44 (2H, d, J=8.1 Hz);

¹⁹F-NMR(CDCl₃) δ −91.1(2F, s);

IR (neat, cm⁻¹) 2978, 1809, 1614, 1364, 1288, 1150, 1103, 1039, 1002,819.

-   2-Fluoro-2-phenyl-ethanol:

¹H-NMR (CDCl₃) δ 1.97 (1H, s), 3.77-3.99 (2H, m), 5.57 (1H, ddd, J=48.8,J=7.8, J=2.9 Hz), 7.34-7.42 (5H, m);

¹⁹F-NMR(CDCl₃) δ −171.1-171.5 (1F, J=48.8, J=29.9, J=19.9 Hz);

IR (KBr, cm⁻¹) 3376, 3030, 2872, 1495, 1454, 1133, 756, 700.

-   1-Chloro-4-fluoromethyl-benzene:

¹H-NMR (CDCl₃) δ 5.31 (2H, d, J=47.6 Hz), 7.31 (2H, d, J=8.3 Hz), 7.37(2H, d, J=8.3 Hz);

¹⁹F-NMR(CDCl₃) δ −208.02 (1F, t, J=47.6 Hz);

IR (neat, cm⁻¹) 1601, 1493, 1410, 1376, 1215, 1091, 985, 840, 804.

-   1-Fluoro-decane:

¹H-NMR (CDCl₃) δ 0.88 (3H, t, J=6.8 Hz), 1.27-1.40 (14H, m), 1.64-1.74(2H, m), 4.43 (2H, dt, J=47.6, J=6.1 Hz);

¹⁹F-NMR(CDCl₃) δ −208.02 (1F, tt, J=47.6, J=25.0 Hz);

IR (neat, cm⁻¹) 2985, 2926, 2856, 1467, 1389, 1046, 1010, 722.

-   1-Difluoromethylsulfanyl-4-methyl-benzene:

¹H-NMR (CDCl₃) 2.37 (3H, s), 6.78 (1H, t, J=57.3 Hz), 7.19(2H, d, J=8.0Hz), 7.46 (2H, d, J=8.0 Hz);

¹⁹F-NMR(CDCl₃) δ −92.23 (2F, d, J=57.3 Hz);

IR (neat, cm⁻¹) 2924, 1597, 1494, 1454, 1320, 1296, 1068, 1020, 818,796.

-   Difluoro-phenylsulfanyl-acetic acid ethyl ester:

¹H-NMR (CDCl₃) δ 1.26 (3H, t, J=7.3 Hz), 4.25, (2H, q, J=7.3 Hz),7.32-7.75 (5H, m);

¹⁹F-NMR(CDCl₃) δ −82.77(2F, s);

IR (neat, cm⁻¹) 2986, 1766, 1474, 1442, 1372, 1296, 1107, 978, 753, 690.

-   4-tert-Butyl-2-(difluoro-methylsulfanyl-methyl)-cyclohexanone:

¹H-NMR (CDCl₃) δ 0.93 (9H, s), 1.25-3.50 (10H, m);

¹⁹F-NMR(CDCl₃) δ −81.56-74.28(2F, m);

IR (neat, cm⁻¹) 2961, 1714, 1440, 1368, 1330, 1175, 1030, 972.

-   (3-Fluoro-propenyl)-benzene:

¹H-NMR (CDCl₃) δ 5.03 (2H, ddd, J=1.2, J=6.1, J=46.8), 6.32-6.42 (1H,m), 6.70 (1H, dd, J=5.1, J=15.9) 7.27-7.42 (5H, m);

¹⁹F-NMR(CDCl₃) δ −211.09 (1F, ddt, J=5.1, J=12.2,J=46.8 Hz);

IR (neat, cm⁻¹) 3027, 2930, 1726, 1495, 1450, 1377, 1114, 967, 746, 692.

-   1-(2-Ethoxy-2,2-difluoro-ethyl)-4-methoxy-benzene:

¹H-NMR (CDCl₃) δ 1.22 (3H, t, J=7.2 Hz), 3.17 (2H, t, J=11.0 Hz), 3.80(3H, s), 3.89 (2H, q, J=7.1 Hz), 6.85 (2H, J=8.8 Hz), 7.21 (2H, J=8.8Hz);

¹⁹F-NMR(CDCl₃) δ −74.94 (2F, t, J=11.0 Hz);

IR (neat, cm⁻¹) 2987, 2838, 1615, 1517, 1347, 1351, 1247, 1179, 1036,823.

-   1-tert-Butyl-4-trifluoromethyl-benzene:

¹H-NMR (CDCl₃) δ 1.34 (9H, s), 7.49 (2H, d, J=8.6 Hz), 7.55 (2H, d,J=8.6 Hz);

¹⁹F-NMR(CDCl₃) δ −62.90 (3F, s);

IR (neat, cm⁻¹) 2968, 1617, 1328, 1166, 1115, 1070, 1015, 840, 706.

-   1-Fluoro-3-oxo-butyric acid butyl ester:

¹H-NMR (CDCl₃) δ 0.95 (3H, t, J=7.3 Hz), 1.36-1.42 (2H, m), 1.66-1.69(2H, m), 2.35 (3H, t, J=4.2 Hz), 5.22 (2H, d, J=49.6 Hz);

¹⁹F-NMR(CDCl₃) δ −193.66 (1F, dq, J=49.3 Hz, J=4.3 Hz);

IR (neat, cm⁻¹) 2964, 2876, 1748, 1735, 1466, 1362, 1261, 1164, 1109,964.

-   2,2-Difluoro-3-oxo-butyric acid butyl ester:

¹H-NMR (CDCl₃) δ 0.95 (3H, t, J=7.5 Hz), 1.37-1.44 (2H, m), 1.66-1.73(2H, m), 2.42 (3H, t, J=1.6 Hz), 4.32 (2H, t, J=6.7 Hz);

¹⁹F-NMR(CDCl₃) δ −114.18 (2F, q, J=1.6);

IR (neat, cm⁻¹) 2964, 2876, 1759, 1465, 1362, 1312, 1134, 1056.

-   2,2-Difluoro-[1,3]dithiane:

¹H-NMR (CDCl₃) δ 2.07-2.15 (2H, m), 3.13-3.17 (2H, m);

¹⁹F-NMR(CDCl₃) δ −63.95 (2F, s);

¹³C-NMR(CDCl₃) δ 23.43, 29.98, 130.77 (t, J_(C−F)=301.1 Hz);

IR (neat, cm⁻¹) 2926, 1677, 1422, 1282, 1081, 998, 921, 873, 811.

-   Difluoro-diphenyl-methane:

¹H-NMR (CDCl₃) δ 7.39-7.52 (10H, m);

¹⁹F-NMR(CDCl₃) δ −89.40 (2F, s);

IR (neat, cm⁻¹) 3067, 1453, 1273, 1223, 1026, 956, 771, 696, 647;

MS m/z: 204 (M⁺); 127, 77;

HRMS: Calc. for C₁₃H₁₀F₂: m/z 204.0751. Found: m/z 204.0755.

-   Difluoro-(4-methylphenyl)-phenyl-methane:

¹H-NMR (CDCl₃) δ 2.37 (3H, s), 7.19-7.51 (9H, m);

¹⁹F-NMR(CDCl₃) δ −88.78 (2F, s);

IR (neat, cm⁻¹) 3068, 2927, 2867, 1450, 1276, 1235, 1046, 958, 619, 582;

MS m/z: 218 (M⁺) 141, 65;

HRMS: Calc. for C₁₄H₁₂F₂: m/z 218.0907. Found: m/z 218.0913.

-   Difluoro-(4-methoxyphenyl)-phenyl-methane:

¹H-NMR (CDCl₃) δ 2.80 (3H, s), 6.89-7.51 (9H, m);

¹⁹F-NMR(CDCl₃) δ −87.41 (2F, s);

IR (neat, cm⁻¹) 3061, 2969, 2936, 2838, 1616, 1514, 1452, 1277, 1224,1056, 957, 616, 588;

MS m/z: 234 (M⁺); 212, 135, 77;

HRMS: Calc. for C₁₄H₁₂F₂O: m/z 234.0856. Found: m/z 234.0856.

-   (1,1-Difluoro-heptyl)-benzene:

¹H-NMR (CDCl₃) δ 0.86 (3H, t, J=6.8 Hz), 1.26-1.33 (6H, m), 1.37-1.44(2H, m), 2.05-2.17 (2H, m), 7.40-7.45 (5H, m);

¹⁹F-NMR(CDCl₃) δ −89.40 (2F, t, J=16.5);

IR (neat, cm⁻¹) 2932, 2859, 1452, 1327, 1168, 1018, 966, 763, 698;

MS m/z: 212 (M⁺); 192, 169, 135, 127, 122, 91, 77;

HRMS: Calc. for C₁₃H₁₈F₂: m/z 212.1377. Found: m/z 212.1374.

-   1-Difluoromethyl-4-methoxy-benzene:

¹H-NMR (CDCl₃) δ 3.77 (3H, s), 6.32 (1H, t, 56 Hz), 6.87-7.38 (4H, d, 9Hz);

¹⁹F-NMR(CDCl₃) δ −108.82 (1H, d, 57 Hz);

IR (neat, cm⁻¹) 3011, 2966, 2842, 1617, 1520, 1308, 1176, 1069, 839;

MS m/z: 158 (M⁺); 139, 127, 115, 108, 95, 77;

HRMS; Calc. for C₈H₉F₂O: m/z 158.0543. Found: m/z 158.0549.

-   1-(1,1-Difluoro-ethyl)-4-nitro-benzene:

¹H-NMR (CDCl₃) δ 1.96 (3H, t, 18 Hz), 7.69-8.31 (4H, q, 18 Hz);

¹⁹F-NMR(CDCl₃) δ −89.71-(−89.56) (2F, q, 18 Hz);

IR (neat, cm⁻¹) 3122, 3089, 3010, 2927, 2862, 1937, 1798, 1612, 634,476;

MS m/z: 187 (M⁺), 172, 141, 101, 91;

HRMS; Calc. for C₈H₇F₂NO₂: m/z 187.0445. Found: m/z 187.0449.

-   9,9-Difluoro-9H-fluorene:

¹H-NMR (CDCl₃) δ 7.32-7.63 (8H, m);

¹⁹F-NMR(CDCl₃) δ −112.14 (2F, s);

IR (neat, cm⁻¹) 1610, 1492, 1453, 1261, 1209, 1165, 939, 653, 585, 423;

MS m/z: 202 (M⁺); 183, 152, 101, 92, 76;

HRMS: Calc. for C₁₃H₈F₂: m/z 202.0594. Found: m/z 202.0594.

-   Difluoro-methylsulfanyl-acetic acid hexyl ester:

¹H-NMR (400 MHz, CDCl₃): δ 0.90 (t, 3H, J=6.8 Hz), 1.25-1.42 (m, 6H),1.69-1.76 (m, 2H), 2.35 (s, 3H), 4.30 (t, 2H, J=6.6 Hz);

¹⁹F-NMR (90 MHz, CDCl₃): δ −86.25 (s, 2F);

IR (neat, cm⁻¹): 2961.16, 2935.13, 2860.88, 1769.37, 1293.04, 1123.33,1000.87;

MS m/z: 226 (M⁺), 142, 129, 97, 85, 43;

HRMS; Calc. for C₁₃H₈F₂: m/z 226.0839. Found: m/z 226.0846.

-   2,2-Difluoro-2-methylsulfanyl-1-phenyl-ethanone:

¹H-NMR (400 MHz, CDCl₃): δ 2.37 (s, 3H), 7.49-8.15 (m, 5H);

¹⁹F-NMR (90 MHz, CDCl₃): δ −82.29 (s, 2F);

IR (neat, cm⁻¹): 0.1704, 1598, 1449, 1270, 1133, 1063, 1004;

MS m/z: 202 (M⁺), 105, 77, 51.

HRMS; Calc. for C₁₃H₈F₂: m/z 202.0264. Found: m/z 202.0266.

-   2,2-Difluoro-1-phenyl-2-phenylsulfanyl-ethanone:

¹H-NMR (400 MHz, CDCl₃): δ 7.37-8.14 (m, 10H);

¹⁹F-NMR (90 MHz, CDCl₃): δ −77.78 (s, 2F);

IR (neat, cm⁻¹): 1704, 1598, 1449, 1272, 1132, 986, 852, 750, 712, 688;

MS m/z: 264(M⁺), 105, 77, 51;

HRMS; Calc. for C₁₃H₈F₂: m/z 264.0420 m/z 264.0426.

-   (1-Fluoro-1-methyl-ethyl)-phenyl-diazene:

¹H-NMR (CDCl₃) δ 1.60 (6H, d, J=19.8 Hz), 7.47 (3H, m), 7.77(2H, m);

¹⁹F-NMR(CDCl₃) δ −120.96 (1F, seventet, J=19.8 Hz);

IR (neat, cm⁻¹) 2292, 1526, 1455, 1366, 1178, 1145, 908, 756, 689.

¹H-NMR (400 MHz, CDCl₃): δ 1.21 (t, 3H, J=7.1 Hz), 4.16 (q, 2H, J=7.2Hz), 6.03 (d, 1H, J=51.7 Hz), 7.34 (d, 2H, J=8.5 Hz), 7.49 (d, 2H, J=8.5Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −159.40 (d, 2F, J=51.7 Hz)

MS: 248(M⁺), 175, 108, 75

C₁₀H₁₀O₂FSCl, Measured Mass 248.0093, Calculated Mass 248.0074

¹H-NMR (400 MHz, CDCl₃): δ 1.30 (t, 3H, J=7.2 Hz), 4.29 (q, 2H, J=7.2Hz), 7.38 (d, 2H, J=8.5 Hz), 7.55 (d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −82.66 (s, 1F)

¹H-NMR (400 MHz, CDCl₃): δ 1.06 (t, 3H, J=7.3 Hz), 1.10 (t, 3H, J=7.1Hz), 2.10-2.36 (m, 2H), 3.97-4.08 (m, 2H), 7.31 (d, 2H, J=8.5 Hz), 7.48(d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −138.53-138.43 (m, 1F)

¹H-NMR (400 MHz, CDCl₃): δ 5.58 (bs, 1H), 6.03 (bs, 1H), 6.07 (d, 1H,J=52.7 Hz), 7.35 (d, 2H, J=8.3 Hz), 7.53 (d, 2H, J=8.3 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −155.46 (d, 1F, J=52.7 Hz)

¹H-NMR (400 MHz, CDCl₃): δ 1.24 (d, 3H, J=6.3 Hz), 1.25 (d, 3H, J=6.3Hz), 1.35 (d, 3H, J=6.8 Hz), 1.42 (d, 3H, J=6.8 Hz), 3.42-3.49 (m, 1H),4.16-4.22 (m, 1H), 6.16 (d, 1H, J=55.9 Hz), 7.33 (d, 2H, J=8.3 Hz), 7.50(d, 2H, J=8.3 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −152.36 (d, 1F, J=55.9 Hz)

¹H-NMR (400 MHz, CDCl₃): δ 1.22 (d, 6H, J=6.59 Hz), 1.43 (d, 6H, J=6.83Hz), 3.47-3.55 (m, 1H), 4.40-4.46 (m, 1H), 7.37 (d, 2H, J=8.5 Hz), 7.56(d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −73.46 (s, 2F)

¹H-NMR (400 MHz, CDCl₃) δ 2.55-2.60 (m, 1H), 2.74-2.86 (m, 1H),4.32-4.45 (m, 2H), 7.36 (d, 2H, J=8.5 Hz), 7.51 (d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −135.76 (d, 1H, J=15.9 Hz)

¹H-NMR (400 MHz, CDCl₃): δ 2.49 (s, 3H), 2.53 (s, 3H), 7.42 (d, 2H,J=8.1 Hz), 7.88 (d, 2H, J=8.1 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −83.83 (s, 2H)

¹H-NMR (400 MHz, CDCl₃) δ 6.18 (d, 1H, J=48.8 Hz), 7.43 (d, 2H, J=8.5Hz), 7.57 (d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −153.90 (d, 1H, J=48.8 Hz)

MS: 201(M+), 143, 63

C₈H₅NFSCl, Measured Mass 200.9798, Calculated Mass 200.9815

¹H-NMR (400 MHz, CDCl₃): δ 1.24 (s, 9H), 6.29 (d, 1H, J=54.2 Hz), 7.34(d, 2H, J=8.5 Hz), 7.48 (d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −157.40 (d, 1F, J=54.2 Hz)

MS: 260(M+), 175, 108, 57

C₁₂H₁₄OFSCl, Measured Mass 260.0421, Calculated Mass 260.0438

¹H-NMR (400 MHz, CDCl₃) δ 1.29 (s, 9H), 7.37 (d, 2H, J=8.5 Hz), 7.53 (d,2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −77.61 (s, 2F)

¹H-NMR (400 MHz, CDCl₃): δ 1.91 (d, 3H, J=18.3 Hz), 3.60 (s, 3H), 7.33(d, 2H, J=8.5 Hz), 7.47 (d, 2H, J=8.5 Hz)

¹⁹F-NMR (400 MHz, CDCl₃): δ −127.24 (q, 1F, J=18.3 Hz)

TABLE 1 Temp. Period of Resultant Yield Example Material (° C.) time (h)Solvent Method product (%) 1 nC₁₃H₂₇—COOH r.t. 12 CH₂Cl₂ A nC₁₃H₂₇—COF75 2 nC₁₃H₂₇—COOH 125 12 No solvent A nC₁₃H₂₇—COF 65 3 nC₁₀H₂₁—OH  80 48Heptane A nC₁₀H₂₁—F 32 4

r.t. 1 CH₂Cl₂ A

83 5

r.t. 1 CH₂Cl₂  A*

6 6

100 1 Heptane A

50 7

 74 1 Heptane A

82 8

 70 1 Heptane  A*

51 9

 63 4 Hexane A

59 10

 63 4 Hexane A

45 11

r.t. 3 Hexane A

60 12

r.t. 5 CH₂Cl₂ B

75 13

r.t. 5 CH₂Cl₂  B*

62 14 PhCOPh 100 12 No solvent A PhCF₂Ph 23 15 (Ph)₂C═NNH₂ r.t. 1 EtOAcD PhCF₂Ph 70 16 (Me)₂C═N—NHPh r.t. 0.5 EtOAc C (Me)₂CF—N═NPh 51 17

r.t. 0.5 EtOAc C

80

TABLE 2 Temp. Period of Resultant Example Material (° C.) time (h)Solvent Method product Yield (%) 18

r.t. 0.5 EtOAc C

52 19

r.t. 1 CH₂Cl₂ D

45 20 phNHNH₂ r.t. 0.5 CH₂Cl₂ A PhF, PhI PhF(30) PhI(40) 21

r.t. 4 CH₂Cl₂  D′

50 22

r.t. 4 CH₂Cl₂  D′

27 23

r.t. 3 CH₂Cl₂ E

11

 6 24

40 1 CH₂Cl₂ A

71 25

60 24 Hexane A

25 26 PhCH═CHCH₂OH r.t. 1 Hexane D PhCH═CHCH₂F 45 PhCHF—CH═CH₂ 22 27

400r.t. 0.50.50.5 (CH₂Cl)₂CH₂Cl₂ FG

3556

TABLE 3 Temp. Period of Resultant Yield Example Material (° C.) time (h)Solvent Method product (%) 28

r.t. 0.5 CH₂Cl₂ A

91 29

r.t. 0.5 CH₂Cl₂   A*²

56 30

r.t. 0.5 CH₂Cl₂  A*

64 31

r.t. 0.5 CH₂Cl₂   A*³

62 32

r.t. 0.5 CH₂Cl₂ A

99 33

r.t. 0.5 CH₂Cl₂ A

87 34

r.t. 0.5 CH₂Cl₂ A

64 35

r.t. 0.5 CH₂Cl₂ A

58 36

r.t. 0.5 CH₂Cl₂ A

96 37

r.t. 2   AcOEt J

30

TABLE 4 Temp. Period of Resultant Yield Example Material (° C.) time (h)Solvent Method product (%) 38

r.t. 2.5 AcOEt H

51 39

r.t. 0.5 CH₂Cl₂ I

91 40

r.t. 126 Heptane A

78 41

40 48 Heptane A

73 42

60 7 Heptane A

81 43

40 32 CHCl₃ A

68 44

r.t. 6 Heptane  A*

59 45 PhCSPh r.t. 1 CH₂Cl₂ I PhCF₂Ph 72 46

r.t. 2.5 AcOEt H

97 47

r.t. 1 CH₂Cl₂   A*²

60 48

r.t. 1 CH₂Cl₂ A

13 49

r.t. 0.5 Hexane   A*²

47

TABLE 5 Period of Resultant Yield Example Material Temp. (° C.) time (h)Solvent Method product (%) 50

40  8 Hexane A

75      15 51

80 72 Heptane A

58 52

40 36 Hexane A

82 53

40  9 Hexane A

89 54

40  4 Hexane A

65 55

40  2 Hexane A

91      4 56

80 72 Heptane A

84 57

40  6 Heptane A

79

TABLE 6 Exam- Temp. Period of Resultant Yield ple Material (° C.) time(h) Solvent Method product (%) 58

40  4 Hexane A

71       7 59

40  5 Hexane A

88 60

80 96 Heptane A

83 61

40  5 Hexane A

82 62

80 90 Heptane A

76 63

60 24 Hexane A

88

In Tables 1 to 6 shown above, “Tol” represents a tolyl group(CH₃—C₆H₄—), “Ph” represents a phenyl group, “Et” represents an ethylgroup, “Me” represents a methyl group, “Bu” represents a butyl group,“Ac” represents an acetyl group, and “iPr” represents an isopropylgroup.

As described above, according to the present invention, it is possibleto fluorinate various kinds of organic compounds having hydrogen atomsand to obtain corresponding fluorine compounds.

INDUSTRIAL APPLICABILITY

According to the present invention, using IF₅, which is an industriallyavailable, nonexplosive, and easy to handle liquid having a boilingpoint at 100.5° C. and a melting point at 9.4° C., it is possible tofluorinate various kinds of organic compounds having hydrogen atoms andto obtain corresponding fluorine compounds.

1. A fluorinating agent for use in fluorinating an organic compoundhaving hydrogen atoms, which comprises IF₅, HF, and an organic baseand/or a room temperature molten salt.
 2. A fluorinating agent for usein fluorinating an organic compound having hydrogen atoms, whichcomprises IF₅ and a room temperature molten salt.
 3. A fluorinatingagent for use in fluorinating an organic compound having hydrogen atoms,which comprises IF₅ and at least one member selected from the groupconsisting of bases and salts.
 4. A fluorinating agent for use influorinating an organic compound having hydrogen atoms, which comprisesIF₅, HF, and triethylamine.
 5. A fluorinating agent according to claim1, which comprises IF₅, HF and an organic base.
 6. A fluorinating agentaccording to claim 1, wherein the organic base is an organic amine.
 7. Afluorinating agent according to claim 6, wherein the organic base is analiphatic amine.
 8. A fluorinating agent according to claim 7, whereinthe organic base is triethylamine.
 9. A fluorinating agent according toclaim 1, which comprises IF₅, HF, and a room temperature molten salt.